Division of Biomedical Science and Biochemistry, Research School of Biology, Australian National University, Acton, ACT, Australia.
Department of Medical Oncology, The Canberra Hospital and ANU Medical School, Australian National University, Garran, ACT, Australia.
Immunol Cell Biol. 2021 Apr;99(4):361-372. doi: 10.1111/imcb.12423. Epub 2020 Nov 22.
Immune checkpoint blockade (ICB) therapies are revolutionary cancer treatments; however, they only benefit about a third of patients. Therefore, extensive research is underway to find methods to improve their therapeutic efficacy. One avenue of study that has recently emerged is to consider the role the gut microbiome plays in therapeutic success. Several high-impact studies have repeatedly shown that the presence, composition and level of diversity of the gut flora directly impact cancer treatment outcome in both mice and patients. These studies have also highlighted the danger of using antibiotics shortly before or during cancer treatments. However, there are still several questions that need to be answered, including which bacteria promote the greatest benefit, the mechanisms by which they act and how we can use this information to influence treatment outcome. In this review, we explain how the gut microbiome was realized to be of such importance and propose hypotheses for why gut flora have such a critical impact on ICB therapeutic success. We also describe a hypothetical mechanism involving bacterial translocation out of the gut and into the tumor, whereby the bacteria act in an adjuvant capacity to facilitate an antitumor response. By highlighting key papers in the field, we hope to hasten research on the subject so as to find a means to improve the therapeutic efficacy of these ground-breaking cancer treatments.
免疫检查点阻断 (ICB) 疗法是革命性的癌症治疗方法；然而，它们只使大约三分之一的患者受益。因此，正在进行广泛的研究以寻找提高其治疗效果的方法。最近出现的一个研究方向是考虑肠道微生物组在治疗成功中的作用。几项高影响力的研究反复表明，肠道菌群的存在、组成和多样性水平直接影响小鼠和患者的癌症治疗结果。这些研究还强调了在癌症治疗前后不久使用抗生素的危险。然而，仍有几个问题需要回答，包括哪些细菌带来最大的益处，它们的作用机制以及我们如何利用这些信息来影响治疗结果。在这篇综述中，我们解释了肠道微生物组如何被意识到具有如此重要性，并提出了为什么肠道菌群对 ICB 治疗成功有如此关键影响的假设。我们还描述了一个涉及细菌从肠道转移到肿瘤的假设机制，其中细菌以佐剂的形式发挥作用，促进抗肿瘤反应。通过强调该领域的关键论文，我们希望加快对该主题的研究，以找到提高这些突破性癌症治疗方法疗效的方法。
